Specific chromosome translocations are characteristic of some leukaemias and solid tumors, and may lead to malignant transformation through the activation or aberrant expression of breakpoint-associated genes [Berger et al., Leukemia Res. Vol. 6:17-26 (1982)]. For example, rearrangements involving human chromosome region 11 q23 are observed in acute leukaemias, especially t(4;11), t(1;11), and t(11;19) in acute lymphoid leukaemias (ALL) [see, for example, Mazo et al., Proc. Natl. Acad. Sci. USA Vol. 87:2112-2116 (1990)]; and t(1;11) t(2;11), t(6;11), t(9;11), t(10;11), t(11;17) and t(X;11) in acute myeloid leukaemia (AML) [see, for example, Sait et al., Cancer Genet. Cytogenet. Vol. 24:181-183 (1987), Feder et al., Cancer Genet. Cytogenet. Vol. 15:143-150), Derre et al., Gene Chromosom. Cancer Vol. 2:341-344 (1990, Hagemeijer et al., Cancer Genet. Cytogenet. Vol. 5:95-105 (1982), and Pui et al., Blood Vol. 69:1289-1293 (1987)].
The frequency of 11 q23 abnormalities is particularly high in leukaemia occurring in infants, accounting for more than 75% of acute leukaemias in those under 12 months of age [see, for example, Abe et al., Cancer Genet. Cytogenet. Vol. 9:139-144 (1983), Chuu et al., Am. J. Hematol. Vol. 34:246-251 (1990), and Gibbons et al., Br. J. Hematol. Vol. 74:264-269 (1990)]. Leukaemia cells isolated from ALLs with the t(4;11) translocation typically exhibit monocytic as well as lymphocytic characteristics, leading to speculation that the gene or genes located at the translocation breakpoint might affect development of an early lymphoid/myeloid precursor stem cell [see Rowley et al., Proc. Natl. Acad. Sci. USA Vol. 87:9358-9362 (1990)].
Previous studies have localized the t(4;11) breakpoint and the t(9;11) breakpoint associated with acute monoblastic (M4-AML) or myelomonocytic (M5-AMML) leukaemias to the same 5.8 kb region of chromosome 11 q23 [see Cimino et al., Cancer Research Vol. 51:6712-6714 (1991)]. Recently, other studies have identified large 11 to 12 kb transcripts arising from the region of the t(4;11) (q21:q23) translocation [see, for example, Ziemin-van der poel et al., Proc. Natl. Acad. Sci. USA Vol. 88:10735-10739 (1991), and Cimino et al., Cancer Research Vol. 52:3811-3813 (1992)].
Accordingly, since consistent chromosome translocations have been associated with a number of human malignancies (including leukaemias, lymphomas and solid tumors), and such translocations may be intimately involved in the molecular pathogenesis of the associated disorders, the development of rapid and effective methods to analyze for the presence of chromosomal aberrations related to such disease states (e.g., translocations involving a chromosomal site of interest) would provide a useful aid in the diagnosis of actual or nascent disease states.